Philippus C. Bornman

Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines

Because acute cholangitis sometimes rapidly progresses to a severe form accompanied by organ dysfunction, caused by the systemic inflammatory response syndrome (SIRS) and/or sepsis, prompt diagnosis and severity assessment are necessary for appropriate management, including intensive care with organ support and urgent biliary drainage in addition to medical treatment. However, because there have been no standard criteria for the diagnosis and severity assessment of acute cholangitis, practical clinical guidelines have never been established. The aim of this part of the Tokyo Guidelines is to propose new criteria for the diagnosis and severity assessment of acute cholangitis based on a systematic review of the literature and the consensus of experts reached at the International Consensus Meeting held in Tokyo 2006. Acute cholangitis can be diagnosed if the clinical manifestations of Charcot’s triad, i.e., fever and/or chills, abdominal pain (right upper quadrant or epigastric), and jaundice are present. When not all of the components of the triad are present, then a definite diagnosis can be made if laboratory data and imaging findings supporting the evidence of inflammation and biliary obstruction are obtained. The severity of acute cholangitis can be classified into three grades, mild (grade I), moderate (grade II), and severe (grade III), on the basis of two clinical factors, the onset of organ dysfunction and the response to the initial medical treatment. “Severe (grade III)” acute cholangitis is defined as acute cholangitis accompanied by at least one new-onset organ dysfunction. “Moderate (grade II)” acute cholangitis is defined as acute cholangitis that is unaccompanied by organ dysfunction, but that does not respond to the initial medical treatment, with the clinical manifestations and/or laboratory data not improved. “Mild (grade I)” acute cholangitis is defined as acute cholangitis that responds to the initial medical treatment, with the clinical findings improved.

Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines.

Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient’s general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient’s general medical condition.

Background: Tokyo Guidelines for the management of acute cholangitis and cholecystitis

There are no evidence-based-criteria for the diagnosis, severity assessment, of treatment of acute cholecysitis or acute cholangitis. For example, the full complement of symptoms and signs described as Charcot’s triad and as Reynolds’ pentad are infrequent and as such do not really assist the clinician with planning management strategies. In view of these factors, we launched a project to prepare evidence-based guidelines for the management of acute cholangitis and cholecystitis that will be useful in the clinical setting. This research has been funded by the Japanese Ministry of Health, Labour, and Welfare, in cooperation with the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. A working group, consisting of 46 experts in gastroenterology, surgery, internal medicine, emergency medicine, intensive care, and clinical epidemiology, analyzed and examined the literature on patients with cholangitis and cholecystitis in order to produce evidence-based guidelines. During the investigations we found that there was a lack of high-level evidence, for treatments, and the working group formulated the guidelines by obtaining consensus, based on evidence categorized by level, according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence of May 2001 (version 1). This work required more than 20 meetings to obtain a consensus on each item from the working group. Then four forums were held to permit examination of the Guideline details in Japan, both by an external assessment committee and by the working group participants (version 2). As we knew that the diagnosis and management of acute biliary infection may differ from country to country, we appointed a publication committee and held 12 meetings to prepare draft Guidelines in English (version 3). We then had several discussions on these draft guidelines with leading experts in the field throughout the world, via e-mail, leading to version 4. Finally, an International Consensus Meeting took place in Tokyo, on 1–2 April, 2006, to obtain international agreement on diagnostic criteria, severity assessment, and management.

Biliary tract obstruction in chronic pancreatitis

Bile duct strictures are a common complication in patients with advanced chronic pancreatitis and have a variable clinical presentation ranging from an incidental finding to overt jaundice and cholangitis. The diagnosis is mostly made during investigations for abdominal pain but jaundice may be the initial clinical presentation. The jaundice is typically transient but may be recurrent with a small risk of secondary biliary cirrhosis in longstanding cases. The management of a bile duct stricture is conservative in patients in whom it is an incidental finding as the risk of secondary biliary cirrhosis is negligible. Initial conservative treatment is advised in patients who present with jaundice as most will resolve once the acute on chronic attack has subsided. A surgical biliary drainage is indicated when there is persistent jaundice for more than one month or if complicated by secondary gallstones or cholangitis. The biliary drainage procedure of choice is a choledocho-jejunostomy which may be combined with a pancreaticojejunostomy in patients who have associated pain. Since many patients with chronic pancreatitis have an inflammatory mass in the head of the pancreas, a Frey procedure is indicated but a resection should be performed when there is concern about a malignancy. Temporary endoscopic stenting is reserved for cholangitis while an expandable metal stent may be indicated in patients with severe co-morbid disease.

Operative management of papillary cystic neoplasms of the pancreas

BACKGROUND Papillary cystic neoplasm (PCN) is a rare malignant tumor of the pancreas that typically occurs in young females and has an excellent prognosis. STUDY DESIGN We report a retrospective review of 12 patients treated during a 16-year period. Pre-, intra-, and postoperative data were evaluated in all patients to determine optimal management with specific reference to surgical strategy. RESULTS All 12 tumors occurred in young women (mean age 22 years, range 14-36 years). Six patients presented with an epigastric mass, and three with severe abdominal pain. The correct diagnosis was made preoperatively in only five patients. Incorrect diagnoses included hepatoma, pancreatic pseudocyst, and hydatid cyst. The PCNs had a mean diameter of 12.5 cm (range 8-20 cm), and occurred in the head (four), neck (three), body (three), and tail (two) of the pancreas. All were resected. Operations performed were pylorus-preserving pancreaticoduodenectomy (three), central pancreatectomy with pancreaticogastrostomy (three), distal pancreatectomy (three), and local resection (three). In one patient two liver metastases were resected in addition to the pancreatic primary. One patient presented with tumor rupture and a major bleed into the lesser sac and died of multiple organ failure after resection. Postoperative complications included a stricture at the hepaticojejunostomy after pancreaticoduodenectomy, which resolved after temporary stenting, and a pancreatic duct fistula after local tumor resection, which required a distal pancreatectomy. Eleven patients are well at followup (mean 6.6 years; range 6 months to 15 years). CONCLUSIONS PCN should be considered in the differential diagnosis of large pancreatic masses, especially in young females. Conservative resection, where technically feasible, is safe and effective and represents the therapy of choice.

Severe necrotizing pancreatitis caused by organophosphate poisoning.

Pancreatitis secondary to organophosphate insecticide toxicity is rare and is believed to follow a subclinical and uneventful course. We report two cases of severe acute pancreatitis complicated by pancreatic necrosis and retroperitoneal sepsis in which the diagnosis was obscured by the systemic effects of organophosphate toxicity. Awareness of this complication should prompt earlier investigation because early diagnosis coupled with timely therapeutic measures may improve patient prognosis.

Variceal Recurrence, Rebleeding, and Survival After Endoscopic Injection Sclerotherapy in 287 Alcoholic Cirrhotic Patients With Bleeding Esophageal Varices

Objective:This study tested the validity of the hypothesis that eradication of esophageal varices by repeated injection sclerotherapy would reduce recurrent variceal bleeding and death from bleeding varices in a high-risk cohort of alcoholic patients with cirrhosis. Summary Background Data:Although banding of esophageal varices is now regarded as the most effective method of endoscopic intervention, injection sclerotherapy is still widely used to control acute esophageal variceal bleeding as well as to eradicate varices to prevent recurrent bleeding. This large single-center prospective study provides data on the natural history of alcoholic cirrhotic patients with bleeding varices who underwent injection sclerotherapy. Methods:Between 1984 and 2001, 287 alcoholic cirrhotic patients (225 men, 62 women; mean age, 51.9 years; range, 24–87 years; Child-Pugh grades A, 39; B, 116; C, 132) underwent a total of 2565upper gastrointestinal endoscopic sessions, which included 353 emergency and 1015 elective variceal injection treatments. Variceal rebleeding, eradication, recurrence, and survival were recorded. Results:Before eradication of varices was achieved, 104 (36.2%) of the 287 patients had a total of 170 further bleeding episodes after the first endoscopic intervention during the index hospital admission. Rebleeding was markedly reduced after eradication of varices. In 147 (80.7%) of 182 patients who survived more than 3 months, varices were eradicated after a mean of 5 injection sessions and remained eradicated in 69 patients (mean follow-up, 34.6 months; range, 1–174 months). Varices recurred in 78 patients and rebled in 45 of these patients. Median follow-up was 32.3 months (mean, 42.1 months; range, 3–198.9 months). Cumulative overall survival by life-table analysis was 67%, 42%, and 26% at 1, 3, and 5 years, respectively. A total of 201 (70%) patients died during follow-up. Liver failure was the most common cause of death. Conclusion:Repeated sclerotherapy eradicates esophageal varices in most alcoholic cirrhotic patients with a reduction in rebleeding. Despite control of variceal bleeding, survival at 5 years was only 26% because of death due to liver failure in most patients.

Guideline for the diagnosis and treatment of chronic pancreatitis

BACKGROUND Chronic pancreatitis (CP) is defined as a continuing inflammatory disease of the pancreas characterised by irreversible morphological changes, often associated with pain and with the loss of exocrine and/or endocrine function that may be clinically relevant. Alcohol is the predominant cause of CP in the western world and is particularly prevalent in South Africa, especially in the indigent patient. CP ranks high among intractable diseases of the gastrointestinal tract. The tendency for substance abuse in the alcohol-induced group poses major psychological and socio-economic problems. OBJECTIVE CP is a disease with significant clinical and pathological heterogeneity. Level 1 evidence to support definitive guidelines for diagnosis, medical management and interventional therapy is lacking. Despite this paucity of robust scientific evidence, it is important to provide some assistance based on the best available evidence as to the current standard of care for CP in the South African context; this will aid all involved in the management of the disease, and includes clinicians, health care managers and funders. SCOPE The guidelines were developed as recommendations addressing the diagnosis, medical management and interventions, both endoscopic and surgical, for the management of a very complex and heterogeneous disease of the pancreas. The recommendations are particularly relevant in the South African context where the predominant patho-aetiological agents are alcohol-associated with smoking. RECOMMENDATIONS The guidelines provide clear recommendations regarding the diagnostic modalities available, both imaging (which includes MRI and endoscopic ultrasound (EUS)) and pancreatic function tests. The section on medical management makes recommendations on the use of analgesics, enzyme replacement and other therapeutic options in the non-interventional management of the majority of patients with CP. The section on interventional procedures identifies the indications and options available for the interventional management of both uncomplicated and complicated CP. The role of endoscopic and surgical modalities is defined, but it is in this context especially that the best available evidence, combined with the experience of the group, influenced the recommendations put forward. Owing to the lack of evidence and the complexity of the disease, it is recommended that, where possible, CP is managed in the context of a multidisciplinary team. VALIDATION The guidelines are based on best practice principles determined by the available evidence and the opinions of the group, which comprised 7 medical and surgical gastroenterologists with significant experience in dealing with patients with chronic pancreatitis in the South African context. The group convened between May 2009 and August 2010 under the auspices of the Hepato-Pancreatico-Biliary Association of South Africa (HPBASA) and the South African Gastroenterology Society (SAGES), and the guidelines are the result of broad consensus within this group. The draft was presented to other experts in this field of endeavour to ensure broader participation and consensus. PLANS FOR GUIDELINE REVISION: HPBASA and SAGES will publish a revised modification of the recommendations when new levels 1 and 2 evidence data are published.

A 15-year experience of injection sclerotherapy in adult patients with extrahepatic portal venous obstruction

ObjectiveThe authors report a 15-year experience with injection sclerotherapy in the management of adult and teenage patients with esophageal varices due to extrahepatic portal venous obstruction (EHPVO). Summary Background DataExtrahepatic portal venous obstruction is an uncommon cause of esophageal varices and is associated with normal liver function. Effective control of variceal bleeding is the major factor influencing survival. The results of surgery have been unsatisfactory, and therefore, more conservative management policies have been adopted. MethodsFifty-five patients with proven EHPVO underwent repeated injection sclerotherapy via either a modified rigid esophagoscope under general anaesthesia or a fiber-optic endoscope under light sedation, using ethanolamine oleate as the sclerosant. ResultsEsophageal varices were eradicated in 44 patients after a median number 6 injections (range 1–17) over a mean of 12.5 months (range 1–48). The mean follow-up was 6.8 years (range 1.1–14.6 years). Eleven patients were admitted on eighteen occasions with bleeding from esophageal varices before eradication and there were seven bleeding episodes in six patients from recurrent varices after initial eradication. Complications related to sclerotherapy included injection site leak (6), stenosis (11) and mucosal ulceration (32) during 362 injection sclerotherapy episodes. Four patients died during the study period. ConclusionsInjection scelotherapy is the treatment of choice in most patients with EHPVO.

Endoscopic balloon dilatation of peptic pyloroduodenal strictures

A through-the-scope endoscopic balloon dilatation technique and acid-reducing medication was used in 46 consecutive patients (median age, 55; range, 21-88 years) with benign gastric outlet obstruction. In five patients, dilatation was not technically possible. In 41 patients, 122 dilatations (median, 2; range, 1-9 per patient) were performed without morbidity. Ninety-four procedures were successful (77%) at the initial attempt (able to pass a 12-mm endoscope into the duodenum at the end of the procedure). Median follow-up in the 41 patients was 19 (range, 1-78) months. Thirteen patients (32%) required subsequent surgery; 8 had delayed operation for persistent symptoms (1-28 months after the first dilatation), 1 had surgery during the initial hospital admission, and 4 required emergency surgery for other ulcer complications (3 perforation, 1 bleeding). Of the 28 patients who had only balloon dilatation and medical therapy, 11 are asymptomatic (4 with active ulceration), 9 have mild symptoms (Visick 2), and 3 have persistent symptoms (Visick 3). One patient was lost to follow-up and four patients have died (one from an ulcer-related complication). Balloon dilatation and sustained acid-reducing therapy with regular endoscopic surveillance should be first-line treatment of peptic pyloroduodenal strictures, because the procedure is safe and is likely to be successful in half of the patients in whom dilatation is technically possible.